It is our working hypothesis that during shock, the stagnation and hypoxia secondary to selective perfusion and compensatory ischemia secondary to hemorrhage, causes an alteration in plasma proteins to form a "pre-toxin"; subsequently, upon the perfusion of lymphoid tissues during therapy, enzymes enter the circulation to cause the activation of the "pre-toxin" to a potent myocardial toxic factor which propagates the shock state terminating in the death of the animal or patient. In this past year we have clearly demonstrated by various bioassay techniques the presence of this toxin in patients suffering from severe shock and some patients undergoing cardiopulmonary bypass. We have furthermore detected this or a similar material in stored blood. Preliminary experiments have shown that we can, by inhibition of the enzyme action and or release, partially circumvent the mortality from severe shock in animals and by particular types of transfusion, prevent many of the difficulties encountered during open heart surgery. Our experiments in this current year are aimed at identification of the toxin as well as continuing our efforts at its detoxification and or the prevention of its appearance in vivo.